Pathophysiology

Wound healing is a continuum of complex interrelated biologic processes at

the molecular level. For descriptive purposes, healing may be divided into the
following three phases:
Inflammatory phase
Proliferative phase
Maturation phase

Inflammatory phase
The inflammatory phase commences as soon as tissue integrity is disrupted
by injury; this begins the coagulation cascade to limit bleeding. Platelets are
the first of the cellular components that aggregate to the wound, and, as a
result of their degranulation (platelet reaction), they release several cytokines
(or paracrine growth factors). These cytokines include platelet-derived growth
factor (PDGF), insulinlike growth factor-1 (IGF-1), epidermal growth factor
(EGF), and fibroblast growth factor (FGF).
Serotonin is also released, which, together with histamine (released by mast
cells), induces a reversible opening of the junctions between the endothelial
cells, allowing the passage of neutrophils and monocytes (which become
macrophages) to the site of injury.
This large cellular movement to the injury site is induced by cytokines
secreted by the platelets (chemotaxis) and by further chemotactic cytokines
secreted by the macrophages themselves once at the site of injury. These
include transforming growth factor alpha (TGF-) and transforming growth
factor beta (TGF-).
Consequently, an inflammatory exudate that contains red blood cells,
neutrophils, macrophages, and plasma proteins, including coagulation
cascade proteins and fibrin strands, fills the wound in a matter of hours.
Macrophages not only scavenge but they also are central to the wound
healing process because of their cytokine secretion.
Proliferative phase
The proliferative phase begins as the cells that migrate to the site of injury,
such as fibroblasts, epithelial cells, and vascular endothelial cells, start to
proliferate and the cellularity of the wound increases. The cytokines involved
in this phase include FGFs, particularly FGF-2 (previously known as basic
FGF), which stimulates angiogenesis and epithelial cell and fibroblast
proliferation.
The marginal basal cells at the edge of the wound migrate across the wound,
and, within 48 hours, the entire wound is epithelialized. In the depth of the
wound, the number of inflammatory cells decreases with the increase in
stromal cells, such as fibroblasts and endothelial cells, which, in turn, continue
to secrete cytokines. Cellular proliferation continues with the formation of
extracellular matrix proteins, including collagen and new capillaries
(angiogenesis). This process is variable in length and may last several weeks.
Maturation phase
In the maturation phase, the dominant feature is collagen. The dense bundle
of fibers, characteristic of collagen, is the predominant constituent of the scar.
Wound contraction occurs to some degree in primary closed wounds but is a
pronounced feature in wounds left to close by secondary intention. The cells
responsible for wound contraction are called myofibroblasts, which resemble
fibroblasts but have cytoplasmic actin filaments responsible for contraction.
The wound continuously undergoes remodeling to try to achieve a state
similar to that prior to injury. The wound has 70-80% of its original tensile
strength at 3-4 months after operation.
Etiology
All surgical wounds are contaminated by microbes, but in most cases,
infection does not develop because innate host defenses are quite efficient in
the elimination of contaminants. A complex interplay between host, microbial,
and surgical factors ultimately determines the prevention or establishment of a
wound infection (see the image below).

Factors that affect surgical

wound healing.
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Microbiology
Microbial factors that influence the establishment of a wound infection are the
bacterial inoculum, virulence, and the effect of the microenvironment. When
these microbial factors are conducive, impaired host defenses set the stage
for enacting the chain of events that produce wound infection.
Most surgical site infections (SSIs) are contaminated by the patient's own
endogenous flora, which are present on the skin, mucous membranes, or
hollow viscera. The traditional microbial concentration quoted as being highly
associated with SSIs is that of bacterial counts higher than 10,000 organisms
per gram of tissue (or in the case of burned sites, organisms per cm2 of
wound). [7]
The usual pathogens on skin and mucosal surfaces are gram-positive cocci
(notably staphylococci); however, gram-negative aerobes and anaerobic
bacteria contaminate skin in the groin/perineal areas. The contaminating
pathogens in gastrointestinal surgery are the multitude of intrinsic bowel flora,
which include gram-negative bacilli (eg, Escherichia coli) and gram-positive
microbes, including enterococci and anaerobic organisms. [8] (See Table 1
below.)
Table 1. Pathogens Commonly Associated with Wound Infections and
Frequency of Occurrence [8] (Open Table in a new window)
Pathogen Frequency (%)

Staphylococcus aureus 20

Coagulase-negative staphylococci 14

Enterococci 12

Escherichia coli 8

Pseudomonas aeruginosa 8

Enterobacter species 7

Proteus mirabilis 3

Klebsiella pneumoniae 3
Other streptococci 3

Candida albicans 3

Group D streptococci 2

Other gram-positive aerobes 2

Bacteroides fragilis 2

Gram-positive organisms, particularly staphylococci and streptococci, account

for most exogenous flora involved in SSIs. Sources of such pathogens include
surgical/hospital personnel and intraoperative circumstances, including
surgical instruments, articles brought into the operative field, and the
operating room air.
The group of bacteria most commonly responsible for SSIs
are Staphylococcus aureus strains. The emergence of resistant strains has
considerably increased the burden of morbidity and mortality associated with
wound infections.
Methicillin-resistant Staphylococcus aureus (MRSA) is proving to be the
scourge of modern-day surgery. Like other strains of S aureus, MRSA can
colonize the skin and body of an individual without causing sickness, and, in
this way, it can be passed on to other individuals unknowingly. Problems arise
in the treatment of overt infections with MRSA because antibiotic choice is
very limited. MRSA infections appear to be increasing in frequency and are
displaying resistance to a wider range of antibiotics. [9]
Of particular concern are the vancomycin intermediate S aureus (VISA)
strains of MRSA. These strains are beginning to develop resistance to
vancomycin, which is currently the most effective antibiotic against MRSA.
This new resistance has arisen because another species of bacteria, called
enterococci, relatively commonly express vancomycin resistance.
Risk factors (other than microbiology)
Decreased host resistance can be due to systemic factors affecting the
patient's healing response, local wound characteristics, or operative
characteristics, as follows:
Systemic factors - Age, malnutrition, hypovolemia, poor tissue perfusion,
obesity, diabetes, steroids, and other immunosuppressants
 Wound characteristics - Nonviable tissue in wound, hematoma, foreign
material (eg, drains and sutures, dead space, poor skin preparation (eg,
shaving), and preexistent sepsis (local or distant)
Operative characteristics - Poor surgical technique; lengthy operation (>2
hours); intraoperative contamination (eg, from infected theater staff and
instruments or inadequate theater ventilation), prolonged preoperative
stay in the hospital, and hypothermia
The type of procedure is a risk factor. Certain procedures are associated with
a higher risk of wound contamination than others. Surgical wounds have been
classified as clean, clean-contaminated, contaminated, and dirty-infected